O-Methylhydroxylamine → Ethyl 1,4-dihydro-1-methoxy-4-oxo-3-quinolinecarboxylate

HRID 1068053Notes

Reaction equation

HRID 1068053 reaction equation
C(O[CH:4]=[C:5]([C:11](=[O:19])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1F)[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.[CH3:20][O:21][NH2:22]>C(O)C>[CH3:20][O:21][N:22]1[C:13]2[C:12](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:11](=[O:19])[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4]1

Participants

4

Reactant 2

HCID 4113O-MethylhydroxylamineHCID 53918296HCID 53918296, compound

Product 1

HCID 21192553Ethyl 1,4-dihydro-1-methoxy-4-oxo-3-quinolinecarboxylateYield 25.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Ethyl 3-ethoxy-2-(2-fluorobenzoyl)-2-propenoate (4.0 g, prepared from ethyl 3-(2-fluorophenyl)-3-oxopropanoate as in Preparation No. 59) and O-methylhydroxylamine (16 mmol, prepared by mixing 1 eq of sodium ethoxide with 1 eq of O-methylhydroxylamine hydrochloride in ethanol) are stirred in ethanol (20 mL) for 1 hour at rt. The mixture is concentrated, diluted with dioxane (75 mL) and re-concentrated to remove any remaining ethanol. The resulting enamine is diluted in dioxane (70 mL) and sodium hydride (60% dispersion, 0.64 g) is added. The mixture is heated to reflux for 2.5 hours, cooled to rt and concentrated in vacuo. The remaining residue is partially dissolved in ethanol (100 mL) and filtered. The filtrate is concentrated in vacuo and chromatographed (7% MeOH/CH2Cl2). The combined fractions are concentrated, leaving a residue which is recrystallized in a 1:1 ether/hexanes mixture to afford 0.95 g of ethyl 1-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate (Mp 120-121° C.) as a white solid.

Workup

  1. concentrationThe mixture is concentrated
  2. additiondiluted with dioxane (75 mL)
  3. concentrationre-concentrated
  4. customto remove any remaining ethanol
  5. additionThe resulting enamine is diluted in dioxane (70 mL)
  6. additionsodium hydride (60% dispersion, 0.64 g) is added
  7. temperatureThe mixture is heated
  8. temperatureto reflux for 2.5 hours
  9. concentrationconcentrated in vacuo
  10. dissolutionThe remaining residue is partially dissolved in ethanol (100 mL)
  11. filtrationfiltered
  12. concentrationThe filtrate is concentrated in vacuo
  13. customchromatographed (7% MeOH/CH2Cl2)
  14. concentrationThe combined fractions are concentrated
  15. customleaving a residue which
  16. customis recrystallized in a 1:1 ether/hexanes mixture

Sources & evidence

ORD record
ord-3a5f4786dd8c49a6ad6429937a39fb7e
Source dataset
uspto-grants-2001_06
Patent number
US06248739B1

Reaction notes

Loading…